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Neurologic autoimmunity and immune checkpoint inhibitors: Autoantibody profiles and outcomes

Sechi, Elia ; Markovic, Svetomir N ; McKeon, Andrew ; Dubey, Divyanshu ; Liewluck, Teerin ; Lennon, Vanda A ; Lopez-Chiriboga, A Sebastian ; Klein, Christopher J ; Mauermann, Michelle ; Pittock, Sean J ; Flanagan, Eoin P ; Zekeridou, Anastasia

Neurology, 2020-10, Vol.95 (17), p.e2442-e2452 [Periódico revisado por pares]

United States: American Academy of Neurology

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  • Título:
    Neurologic autoimmunity and immune checkpoint inhibitors: Autoantibody profiles and outcomes
  • Autor: Sechi, Elia ; Markovic, Svetomir N ; McKeon, Andrew ; Dubey, Divyanshu ; Liewluck, Teerin ; Lennon, Vanda A ; Lopez-Chiriboga, A Sebastian ; Klein, Christopher J ; Mauermann, Michelle ; Pittock, Sean J ; Flanagan, Eoin P ; Zekeridou, Anastasia
  • Assuntos: Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Autoantibodies - analysis ; Autoimmune Diseases - immunology ; Autoimmunity - immunology ; Disease Progression ; Female ; Humans ; Immunotherapy - methods ; Male ; Middle Aged ; Neoplasms - therapy ; Nervous System Diseases - immunology ; Neuromuscular Diseases - immunology ; Neuromuscular Diseases - physiopathology ; Retrospective Studies ; Treatment Outcome
  • É parte de: Neurology, 2020-10, Vol.95 (17), p.e2442-e2452
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
  • Descrição: OBJECTIVETo describe neural autoantibody profiles and outcomes in patients with neurologic autoimmunity associated with immune checkpoint inhibitor (ICI) cancer immunotherapy. METHODSIn this retrospective descriptive study, 63 patients with ICI-related neurologic autoimmunity were included39 seen at the Mayo Clinic Neurology Department (clinical cohort) and 24 whose serum/CSF was referred to the Mayo Clinic Neuroimmunology Laboratory for autoantibody testing. Serum/CSF samples were tested for neural-specific autoantibodies. Predictors of unfavorable outcome (residual adverse event severity grade ≥3) were explored (logistic regression). RESULTSMedian age at neurologic symptom onset was 65 years (range 31–86); 40% were female. Neurologic manifestations were CNS-restricted (n = 26), neuromuscular (n = 30), combined (n = 5), or isolated retinopathy (n = 2). Neural-specific autoantibodies were common in patients with CNS involvement (7/13 [54%] in the unbiased clinical cohort) and included known or unidentified neural-restricted specificities. Only 11/31 patients with CNS manifestations had neuroendocrine malignancies typically associated with paraneoplastic autoimmunity. Small-cell lung cancer (SCLC)–predictive antibodies were seen in 3 patients with non-neuroendocrine tumors (neuronal intermediate filament immunoglobulin G [IgG] and antineuronal nuclear antibody 1 with melanoma; amphiphysin IgG with non-SCLC). A median of 10 months from onset (range, 0.5–46), 14/39 in the clinical cohort (36%) had unfavorable outcomes; their characteristics were age ≥70 years, female, CNS involvement, lung cancer, higher initial severity grade, and lack of systemic autoimmunity. By multivariate analysis, only age remained independently associated with poor outcome (p = 0.01). Four of 5 patients with preexistent neurologic autoimmunity experienced irreversible worsening after ICI. CONCLUSIONSNeural-specific autoantibodies are not uncommon in patients with ICI-related CNS neurologic autoimmunity. Outcomes mostly depend on the pre-ICI treatment characteristics and clinical phenotype.
  • Editor: United States: American Academy of Neurology
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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